scholarly journals Extracellular Vesicles in Immune System Regulation and Type 1 Diabetes: Cell-to-Cell Communication Mediators, Disease Biomarkers, and Promising Therapeutic Tools

2021 ◽  
Vol 12 ◽  
Author(s):  
Giuseppina Emanuela Grieco ◽  
Daniela Fignani ◽  
Caterina Formichi ◽  
Laura Nigi ◽  
Giada Licata ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Biological Fluids ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Disease Biomarkers

Extracellular vesicles (EVs) are generated by cells of origin through complex molecular mechanisms and released into extracellular environment. Hence, the presence of EVs has been described in multiple biological fluids and in most cases their molecular cargo, which includes non-coding RNAs (ncRNA), messenger RNAs (mRNA), and proteins, has been reported to modulate distinct biological processes. EVs release and their molecular cargo have been demonstrated to be altered in multiple diseases, including autoimmune diseases. Notably, numerous evidence showed a relevant crosstalk between immune system and interacting cells through specific EVs release. The crosstalk between insulin-producing pancreatic β cells and immune system through EVs bidirectional trafficking has yet started to be deciphered, thus uncovering an intricate communication network underlying type 1 diabetes (T1D) pathogenesis. EVs can also be found in blood plasma or serum. Indeed, the assessment of circulating EVs cargo has been shown as a promising advance in the detection of reliable biomarkers of disease progression. Of note, multiple studies showed several specific cargo alterations of EVs collected from plasma/serum of subjects affected by autoimmune diseases, including T1D subjects. In this review, we discuss the recent literature reporting evidence of EVs role in autoimmune diseases, specifically focusing on the bidirectional crosstalk between pancreatic β cells and immune system in T1D and highlight the relevant promising role of circulating EVs as disease biomarkers.

scholarly journals Genetic Variants Predisposing Most Strongly to Type 1 Diabetes Diagnosed Under Age 7 Years Lie Near Candidate Genes That Function in the Immune System and in Pancreatic β-Cells

Diabetes Care ◽  
2019 ◽  
Vol 43 (1) ◽  
pp. 169-177 ◽  
Author(s):  
Jamie R.J. Inshaw ◽  
Antony J. Cutler ◽  
Daniel J.M. Crouch ◽  
Linda S. Wicker ◽  
John A. Todd
Keyword(s):  
Type 1 Diabetes ◽  
Immune System ◽  
Candidate Genes ◽  
Genetic Variants ◽  
Β Cells ◽  
Pancreatic Β Cells

Formation of pancreatic β-cells from precursor cells contributes to the reversal of established type 1 diabetes

2021 ◽  
pp. 104360
Author(s):  
Tobechukwu K. Ukah ◽  
Alexis N. Cattin-Roy ◽  
George E. Davis ◽  
Habib Zaghouani
Keyword(s):  
Type 1 Diabetes ◽  
Precursor Cells ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Nonlinear Analysis for a Type-1 Diabetes Model with Focus on T-Cells and Pancreatic β-Cells Behavior

2020 ◽  
Vol 25 (2) ◽  
pp. 23
Author(s):  
Diana Gamboa ◽  
Carlos E. Vázquez ◽  
Paul J. Campos
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cell Population ◽  
Closed Loop ◽  
Pancreatic Β Cell ◽  
Activated Macrophages ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

Type-1 diabetes mellitus (T1DM) is an autoimmune disease that has an impact on mortality due to the destruction of insulin-producing pancreatic β -cells in the islets of Langerhans. Over the past few years, the interest in analyzing this type of disease, either in a biological or mathematical sense, has relied on the search for a treatment that guarantees full control of glucose levels. Mathematical models inspired by natural phenomena, are proposed under the prey–predator scheme. T1DM fits in this scheme due to the complicated relationship between pancreatic β -cell population growth and leukocyte population growth via the immune response. In this scenario, β -cells represent the prey, and leukocytes the predator. This paper studies the global dynamics of T1DM reported by Magombedze et al. in 2010. This model describes the interaction of resting macrophages, activated macrophages, antigen cells, autolytic T-cells, and β -cells. Therefore, the localization of compact invariant sets is applied to provide a bounded positive invariant domain in which one can ensure that once the dynamics of the T1DM enter into this domain, they will remain bounded with a maximum and minimum value. Furthermore, we analyzed this model in a closed-loop scenario based on nonlinear control theory, and proposed bases for possible control inputs, complementing the model with them. These entries are based on the existing relationship between cell–cell interaction and the role that they play in the unchaining of a diabetic condition. The closed-loop analysis aims to give a deeper understanding of the impact of autolytic T-cells and the nature of the β -cell population interaction with the innate immune system response. This analysis strengthens the proposal, providing a system free of this illness—that is, a condition wherein the pancreatic β -cell population holds and there are no antigen cells labeled by the activated macrophages.

scholarly journals Dextran Sulfate Protects Pancreatic β-Cells, Reduces Autoimmunity, and Ameliorates Type 1 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (8) ◽  
pp. 1692-1707
Author(s):  
Geming Lu ◽  
Francisco Rausell-Palamos ◽  
Jiamin Zhang ◽  
Zihan Zheng ◽  
Tuo Zhang ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Dextran Sulfate ◽  
Β Cells ◽  
Pancreatic Β Cells

Bile acid-polymer-probucol microparticles: protective effect on pancreatic β-cells and decrease in type 1 diabetes development in a murine model

2019 ◽  
Vol 24 (10) ◽  
pp. 1272-1277 ◽  
Author(s):  
Armin Mooranian ◽  
Nassim Zamani ◽  
Giuseppe Luna ◽  
Hesham Al-Sallami ◽  
Momir Mikov ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Bile Acid ◽  
Protective Effect ◽  
Murine Model ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Diabetes Development

scholarly journals Probiotics and Prebiotics for the Amelioration of Type 1 Diabetes: Present and Future Perspectives

2019 ◽  
Vol 7 (3) ◽  
pp. 67 ◽  
Author(s):  
Sidharth Mishra ◽  
Shaohua Wang ◽  
Ravinder Nagpal ◽  
Brandi Miller ◽  
Ria Singh ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Immune System ◽  
Gut Microbiota ◽  
Adaptive Immune Response ◽  
Early Years ◽  
Autoimmune Response ◽  
Β Cells ◽  
Environmental Interactions

Type 1-diabetes (T1D) is an autoimmune disease characterized by immune-mediated destruction of pancreatic beta (β)-cells. Genetic and environmental interactions play an important role in immune system malfunction by priming an aggressive adaptive immune response against β-cells. The microbes inhabiting the human intestine closely interact with the enteric mucosal immune system. Gut microbiota colonization and immune system maturation occur in parallel during early years of life; hence, perturbations in the gut microbiota can impair the functions of immune cells and vice-versa. Abnormal gut microbiota perturbations (dysbiosis) are often detected in T1D subjects, particularly those diagnosed as multiple-autoantibody-positive as a result of an aggressive and adverse immunoresponse. The pathogenesis of T1D involves activation of self-reactive T-cells, resulting in the destruction of β-cells by CD8+ T-lymphocytes. It is also becoming clear that gut microbes interact closely with T-cells. The amelioration of gut dysbiosis using specific probiotics and prebiotics has been found to be associated with decline in the autoimmune response (with diminished inflammation) and gut integrity (through increased expression of tight-junction proteins in the intestinal epithelium). This review discusses the potential interactions between gut microbiota and immune mechanisms that are involved in the progression of T1D and contemplates the potential effects and prospects of gut microbiota modulators, including probiotic and prebiotic interventions, in the amelioration of T1D pathology, in both human and animal models.

scholarly journals The structural and functional recovery of pancreatic β-cells in type 1 diabetes mellitus induced mesenchymal stem cell-conditioned medium

2016 ◽  
Vol 9 (5) ◽  
pp. 535-539 ◽  
Author(s):  
Widagdo Sri Nugroho ◽  
Dwi Liliek Kusindarta ◽  
Heru Susetya ◽  
Ida Fitriana ◽  
Guntari Titik Mulyani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Type 1 Diabetes Mellitus ◽  
Functional Recovery ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Cell Conditioned Medium

scholarly journals Expression of the B7.1 Costimulatory Molecule on Pancreatic β Cells Abrogates the Requirement for CD4 T Cells in the Development of Type 1 Diabetes

2004 ◽  
Vol 173 (2) ◽  
pp. 787-796 ◽  
Author(s):  
Evis Havari ◽  
Ana Maria Lennon-Dumenil ◽  
Ludger Klein ◽  
Devon Neely ◽  
Jacqueline A. Taylor ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Cd4 T Cells ◽  
Costimulatory Molecule ◽  
Β Cells ◽  
Pancreatic Β Cells

scholarly journals Potential Mimicry of Viral and Pancreatic β Cell Antigens Through Non-Spliced and cis-Spliced Zwitter Epitope Candidates in Type 1 Diabetes

2021 ◽  
Vol 12 ◽  
Author(s):  
Michele Mishto ◽  
Artem Mansurkhodzhaev ◽  
Teresa Rodriguez-Calvo ◽  
Juliane Liepe
Keyword(s):  
Type 1 Diabetes ◽  
T Cell ◽  
Viral Infections ◽  
Hla Class I ◽  
Class I ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

Increasing evidence suggests that post-translational peptide splicing can play a role in the immune response under pathological conditions. This seems to be particularly relevant in Type 1 Diabetes (T1D) since post-translationally spliced epitopes derived from T1D-associated antigens have been identified among those peptides bound to Human Leucocyte Antigen (HLA) class I and II complexes. Their immunogenicity has been confirmed through CD4+ and CD8+ T cell-mediated responses in T1D patients. Spliced peptides theoretically have a large sequence variability. This might increase the frequency of viral-human zwitter peptides, i.e. peptides that share a complete sequence homology irrespective of whether they originate from human or viral antigens, thereby impinging upon the discrimination between self and non-self antigens by T cells. This might increase the risk of autoimmune responses triggered by viral infections. Since enteroviruses and other viral infections have historically been associated with T1D, we investigated whether cis-spliced peptides derived from selected viruses might be able to trigger CD8+ T cell-mediated autoimmunity. We computed in silico viral-human non-spliced and cis-spliced zwitter epitope candidates, and prioritized peptide candidates based on: (i) their binding affinity to HLA class I complexes, (ii) human pancreatic β cell and medullary thymic epithelial cell (mTEC) antigens’ mRNA expression, (iii) antigen association with T1D, and (iv) potential hotspot regions in those antigens. Neglecting potential T cell receptor (TCR) degeneracy, no viral-human zwitter non-spliced peptide was found to be an optimal candidate to trigger a virus-induced CD8+ T cell response against human pancreatic β cells. Conversely, we identified some zwitter peptide candidates, which may be produced by proteasome-catalyzed peptide splicing, and might increase the likelihood of pancreatic β cells recognition by virus-specific CD8+ T cell clones, therefore promoting β cell destruction in the context of viral infections.

scholarly journals Dextran Sulfate Protects Pancreatic β-Cells, Reduces Autoimmunity and Ameliorates Type 1 Diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Geming Lu ◽  
Francisco Rausell-Palamos ◽  
Jiamin Zhang ◽  
Zihan Zheng ◽  
...  
Keyword(s):  
T Cells ◽  
Type 1 Diabetes ◽  
Heparan Sulfate ◽  
Dextran Sulfate ◽  
Nod Mice ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells

A failure in self-tolerance leads to autoimmune destruction of pancreatic β-cells and type 1 diabetes (T1D). Low molecular weight dextran sulfate (DS) is a sulfated semi-synthetic polysaccharide with demonstrated cytoprotective and immunomodulatory properties <i>in vitro</i>. However, whether DS can protect pancreatic β-cells, reduce autoimmunity and ameliorate T1D is unknown. Here we report that DS, but not dextran, protects human β-cells against cytokine-mediated cytotoxicity <i>in vitro</i>. DS also protects mitochondrial function and glucose-stimulated insulin secretion and reduces chemokine expression in human islets in a pro-inflammatory environment. Interestingly, daily treatment with DS significantly reduces diabetes incidence in pre-diabetic non-obese diabetic (NOD) mice, and most importantly, reverses diabetes in early-onset diabetic NOD mice. DS decreases β-cell death, enhances islet heparan sulfate (HS)/heparan sulfate proteoglycan (HSPG) expression and preserves β-cell mass and plasma insulin in these mice. DS administration also increases the expression of the inhibitory co-stimulatory molecule programmed death-1 (PD-1) in T-cells, reduces interferon-γ+ CD4+ and CD8+ T-cells and enhances the number of FoxP3+ cells. Collectively, these studies demonstrate that the action of one single molecule, DS, on β-cell protection, extracellular matrix preservation and immunomodulation can reverse diabetes in NOD mice highlighting its therapeutic potential for the treatment of T1D.

Sign in / Sign up

Export Citation Format

Share Document